Tumor Biology

, Volume 37, Issue 5, pp 5999–6006 | Cite as

Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway

  • Shirin Hasan
  • Nida Suhail
  • Nayeem Bilal
  • Ghulam Md. Ashraf
  • Syed Kashif Zaidi
  • Sultan AlNohair
  • Naheed Banu
Original Article


Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.


Carcinogenesis Chronic unpredictable stress DMBA DNA damage Oxidative stress Pomegranate 



The authors are grateful to Aligarh Muslim University, Aligarh, for providing necessary facilities. The financial assistance in the form of a scholarship to the authors from the University Grants Commission (UGC), New Delhi, is thankfully acknowledged.

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Shirin Hasan
    • 1
    • 2
  • Nida Suhail
    • 1
    • 6
  • Nayeem Bilal
    • 1
  • Ghulam Md. Ashraf
    • 1
    • 7
  • Syed Kashif Zaidi
    • 3
  • Sultan AlNohair
    • 4
  • Naheed Banu
    • 1
    • 5
  1. 1.Department of Biochemistry, Faculty of Life SciencesAligarh Muslim UniversityAligarhIndia
  2. 2.Department of SurgeryLoyola University ChicagoMaywoodUSA
  3. 3.Center of Excellence in Genomic Medicine ResearchKing Abdulaziz UniversityJeddahSaudi Arabia
  4. 4.Department of Family and Community Medicine, College of MedicineQassim UniversityQassimSaudi Arabia
  5. 5.College of Medical RehabilitationQassim UniversityBuraydahSaudi Arabia
  6. 6.Department of Biochemistry, Faculty of Applied Medical SciencesNorthern Border UniversityArarSaudi Arabia
  7. 7.King Fahd Medical Research CenterKing Abdulaziz UniversityJeddahSaudi Arabia

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